The proposed project explores how researchers in the new and growing arena of gene- environment interaction (GxE) research operationalize the concept of a human population. The proposed project will add critical information about how traditional epidemiologists and genetic epidemiologists, using different kinds of data, work together to operationalize groups in their biomedical studies of disease. This phase of our research will investigate the challenges and complexities faced by researchers during a) the design of populations when environmental variables are integrated into genetics studies, and b) when research centers pool samples along similarities in genetics or environmental exposures. The project will examine the social and ethical dimensions of analyses and results generated by GxE research. This is particularly important as these GxE studies aim to integrate genetic data with environmental variables that may be connected to socio-cultural categories like race and ethnicity, including diet and lifestyle. The GxE research sites to be studied have longitudinal information on environmental exposures from about 70,000 individuals of mostly under-represented racial and ethnic backgrounds, and have recently added DNA and tissue materials. This combination of GxE variables, diverse populations, and the large size of the cohort makes their repository one of the most desirable in the US for samples for GxE studies. The research methodology for the proposed study involves primarily ethnographic observation of work processes in these laboratories, interviews with scientists, and documentary analyses. This project will provide a broader base of empirical information from which the scientific community, bioethicists and policy makers can understand the potential impact of using different frameworks for grouping people and defining populations in biomedicine. Its findings will be useful to scientists in efforts to recognize and deliberate about their usage of concepts of population in future studies. PUBLIC HEALTH RELEVANCE: The proposed project will investigate the conceptualization and operationalization of concepts of population in studies of gene-environment interactions in human genetic epidemiology research. The project will analyze the practices and problems faced by researchers as they work to compare genomic data with information on environmental factors to understand gene-environment interactions. Some of the challenges faced involve analyzing pooled data collected using different categories. The aim of the proposed project is to provide information and analyses about different uses and notions of population in biomedicine, which will be useful for improving the reliability and relevance of public health-related gene-environment interaction studies for different individuals and groups.